Prognostic values of EORTC QLQ-C30 and QLQ-HCC18 index-scores in patients with hepatocellular carcinoma – clinical application of health-related quality-of-life data

This is the first prospective study to demonstrate that the prognostic significance of QLQ-C30 was not limited to advance-stage HCC patients but valid for newly diagnosed patients with various stages of disease. Worse scores in physical functioning, pain and financial difficulties were associated with shorter OS in dichotomized variable analyses, while worse scores in physical functioning and pain were significant in continuous variable analyses.

This is also the first prospective study to demonstrate that baseline QLQ-HCC18 is a significant prognostication tool for OS in newly diagnosed HCC patients. Worse dichotomized score in fatigue was an independent prognostic factor for shorter OS, while worse continuous scores in fatigue and pain were also significant poor prognostic factors.

Physical functioning domain in the present study concurred with previous findings by Yeo et al. [1] (where physical and role functioning, appetite loss were significant prognostic factors for OS), and Diouf et al. [3] (where physical [dichotomized] or role functioning [continuous] were significant factors).

The HRQOL factors identified in this study varied from previous studies and could be due to a number of reasons. Firstly, patient populations were different, our study involved early as well as advanced stage HCC patients while prior studies involved only advanced stage disease. Secondly, patients of different cultural backgrounds could have different HRQOL perceptions. Thirdly, studies conducted more recently carried more available treatment options than earlier era, which may have led to differences in perception of disease and thus HRQOL. Fourthly, although different studies might utilize the same HRQOL tool, the methodologies of data analysis varied across trials.

The failure to identify consistent HRQOL factors for OS across studies makes clinically meaningful utilization of HRQOL for prognostication difficult. On the other hand, using simple algorithm and calculation, C30 and HCC18 index-scores could be derived from the raw data of all domains and items within QLQ-C30 and QLQ-HCC18 respectively. It is a meaningful representation of the overall HRQOL of an individual patient.

The C30 and HCC18 index-scores were proven to be highly significant prognostic factors for survival, and were more significant than any individual HRQOL factor, whether continuous or dichotomized. When the index-scores were stratified into subgroups, distinct OS outcomes could be identified. Clinical use of either C30 or HCC18 index-score at baseline provides another means of survival estimation in patients with newly diagnosed HCC apart from conventional staging systems. Index-score could be calculated in the clinical setting in a user-friendly manner. With the aid of modern computer technology, patients may be able to self-administer the QLQ-C30 or QLQ-HCC18 questionnaire and have the respective index-score generated by handheld devices.

One limitation of this study was the lack of a separate patient population, for instance, that of a different geographical or cultural background, to allow external validation of the multivariate cox proportional hazard models. However, bootstrapping has enabled internal validation of the multivariate models.

HRQOL assessment is important to aid clinical management in HCC patients. Being an aggressive disease, patients commonly present at advanced stage when treatment option is limited, of modest benefit and associated with disabling toxicities. HRQOL assessment enables the identification of symptoms/problems, whereby symptom control and psychosocial support measures could be offered as part of palliative care in parallel with anti-neoplastic therapy.

HRQOL tools could further be utilized to provide prognostic information. HRQOL analyses may potentially supplement available clinical staging systems in prognostication. External validation of the role of QLQ-C30 and HCC18 index-scores in prognostication in HCC patients is warranted. Index-scoring may prove useful in HRQOL research for other cancer types and further studies are encouraged.